By late April 2020, public discourse in the U.S. had shifted toward the idea of using more targeted case-based mitigation tactics (e.g., contact tracing) to combat COVID-19 transmission while allowing for the safe “re-opening” of society, in an effort to reduce the social, economic, and political ramifications associated with stricter approaches. Expanded tracing-testing efforts were touted as a key solution that would allow for a precision approach, thus preventing economies from having to shut down again. However, it is now clear that many regions of the U.S. were unable to mount robust enough testing-tracing programs to prevent major resurgences of disease. This viewpoint offers a discussion of why testing-tracing efforts failed to sufficiently mitigate COVID-19 across much of the nation, with the hope that such deliberation will help the U.S. public health community better plan for the future.

Background Antibodies to PD-1 and CTLA-4 may perturb HIV persistence during antiretroviral therapy (ART) by reversing HIV-latency and/or boosting HIV-specific immunity leading to clearance of infected cells. We tested this hypothesis in a clinical trial of anti-PD-1 alone or in combination with anti-CTLA-4 in people living with HIV (PLWH) and cancer. Methods This was a substudy of the AIDS Malignancy Consortium-095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti-PD-1) with or without ipilimumab (anti-CTLA-4). In samples obtained pre-infusion and one and seven days after the first and fourth dose of immune checkpoint blockade (ICB), we quantified cell-associated unspliced (CA-US) HIV-RNA and HIV-DNA. Plasma HIV-RNA was quantified during the first treatment cycle. Quantitative viral outgrowth assay (QVOA) to estimate the frequency of replication-competent HIV was performed before and after ICB for participants with samples available. Results Of forty participants, 33 received nivolumab and seven nivolumab plus ipilimumab. Whereas CA-US HIV RNA did not change with nivolumab monotherapy, we detected a median 1.44 fold-increase (IQR 1.16–1.89) after the first dose of nivolumab and ipilimumab combination therapy (P=0.031). There was no decrease in the frequency of cells containing replication-competent HIV, but in the two individuals on combination ICB for whom we had longitudinal QVOA, we detected decreases of 97% and 64% compared to baseline. Conclusion Anti-PD-1 alone showed no effect on HIV-latency or the latent HIV-reservoir, but the combination of anti-PD-1 and anti-CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV.

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Human papillomavirus (HPV) associated anal and oropharyngeal cancer incidence has increased in recent years among US women. However, trends in incidence and burden (annual number of cases) of non-cervical HPV-associated cancers relative to cervical cancer remain unclear. Using the 2001-2017 US cancer statistics dataset, we evaluated contemporary incidence trends and burden (annual number of cases) of HPV-associated cancers among women by anatomic site, race/ethnicity, and age. Overall, cervical cancer incidence plateaued among White women but continued to decline among Blacks and Hispanics. Anal cancer incidence surpassed cervical cancer incidence among White women aged 65-74 years old (8.6 and 8.2 per 100,000 in 2015) and ≥75 years old (6.2 and 6.0 per 100,000 in 2014). The non-cervical cancer burden (n = 11,871) surpassed the cervical cancer burden (n = 11,527) in 2013. Development of efficacious screening strategies for non-cervical cancers and continued improvement in cervical cancer prevention is needed to combat HPV-associated cancers among women.

More than 80% of global hepatocellular carcinoma (HCC) patients are estimated to occur in sub-Saharan Africa (SSA) and Eastern Asia. The most common risk factor of HCC in SSA is chronic hepatitis B virus (HBV) infection, with the incidence highest in West Africa. HBV is highly endemic in SSA and is perpetuated by incomplete adherence to birth dose immunization, lack of longitudinal follow-up care, and impaired access to antiviral therapy. HBV may directly cause HCC through somatic genetic alterations or indirectly through altered liver function and liver cirrhosis. Other risk factors of HCC in SSA include aflatoxins and, to a lesser extent, African iron overload. HIV plus HBV co-infection increases the risk of developing HCC and is increasingly becoming more common because of improving the survival of patients with HIV infection. Compared with the rest of the world, patients with HCC in SSA have the lowest survival. This is partly due to the late presentation of HCC with advanced symptomatic disease as a result of underdeveloped surveillance practices. Moreover, access to care and resource limitations further limit outcomes for the patients who receive a diagnosis in SSA. There is a need for multipronged strategies to decrease the incidence of HCC and improve its outcomes in SSA.